Human immunodeficiency virus type 1 (HIV-1) is the etiological agent that causes acquired immunodeficiency syndrome (AIDS). According to the AIDS Epidemic Update (UNAIDS, December 2007) approximately 36 million people are living with HIV-1, particularly in Sub-Saharan Africa and South-East Asia. The introduction of highly active anti-retroviral therapy (HAART) has significantly contributed to the decreased morbidity and mortality among HIV-1 infected people; however, the patient's developed drug resistance severely limits treatment options available. The developed resistance and the failure of several therapies in recent clinical trials have reinforced the critical need to identify and utilize newer targets to develop new classes of anti-HIV-1 drugs that broaden the scope of treatment and reduce development of treatment resistant HIV-1 variants.
HIV-1 infection involves the attachment of the virus to the host cell, reverse transcription of genetic material from viral RNA to DNA, integration of viral DNA with host DNA, replication of viral RNA from DNA, translation of viral RNA to create viral proteins, cleavage of viral proteins, assembly and packaging of viral proteins, and budding from the host cell.
HIV-1 infection of a host immune cell first requires attachment of the virus to the cell membrane. On the surface membrane of all living cells are complex protein structures called “receptors”. A receptor is often compared to a lock into which a specific key or “ligand” will fit. Attachment of the virions to receptors on the host membrane enables fusion and the viral contents, including viral RNA, will empty into the cell's cytoplasm. Like other viruses that infect human cells, HIV-1 commandeers the host's machinery to make multiple copies of itself. Once the RNA has been copied and translated into proteins, the viral RNA and associated proteins are packaged and released from the host cell, taking with them a piece of the cell membrane.
There are only nine genes in the HIV-1 genome. These genes have the code necessary to produce structural proteins, such as the viral core and enzymes like reverse transcriptase, integrase, and protease. One of the most important genes, the gag gene, encodes the Gag protein, the critical structure protein of HIV-1. In human cells infected by HIV-1, the viral Gag protein directs assembly of nascent viral particles at the plasma membrane, and thus, is a good target for disruption of retroviral assembly.